Locally Advanced Rectal CancerPhase 2nECTNCT03040180
Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer
A Phase 2 study testing Electrochemotherapy with bleomycin and EndoVE in people with Locally Advanced Rectal Cancer and Electrochemotherapy, run by Zealand University Hospital at 2 sites in Denmark.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Rectal Cancer, Electrochemotherapy, Neoadjuvant Therapy
- What is being tested?
- Electrochemotherapy with bleomycin and EndoVE
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesDenmark
- Study dates
- Jan 2017to Sep 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must be mentally capable of understanding the information given.
- Patients must give written informed consent.
- Men or women aged at least 18 years.
- Histologically verified rectal tumor (adenocarcinoma)
- Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with neoadjuvant therapy followed by surgical excision (UICC stadium II-III).
- ASA class I-III (Classification of the American Society of Anesthesiology)
Who cannot join
- Coagulation disorders
- Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
- Patients with ICD or pacemaker units.
- Patients with epilepsy.
- Pregnancy or lactation/breastfeeding.
- Patients with known Hepatitis B/C or HIV infection.
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- Patients who have undergone treatment with bevacizumab within 4 weeks prior to enrolment in this trial.
- Patients with concomitant use of phenytoin.
- Patients with concomitant use of clozapine.
- Concurrent treatment with an investigational medicinal product.
- Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study recruitments.
- Patients with contraindications for PET/MRI scan:
- Advanced tumor stage, UICC stage IV.
- Acute pulmonary infection.
- Medical history of severe pulmonary disease.
- Previous allergic reactions to bleomycin.
- Previous cumulative dose of bleomycin exceeding 250.000 IU/m2.
- Pre-existing renal dysfunction. Creatinine clearance < 40 ml/min.
- Platelet count ≤50 mia/l.
- Prothrombin time ≥ 40 sec
- Patients registered in the Danish Tissue Register (Vaevsanvendelsesregistret)
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites, 2 recruiting
- Recruiting
Department of Oncology
Herlev, Capitol Region, 2730
Julie Gehl, MD, DMSc, +45 38683868, karen.julie.gehl@regionh.dk
- Recruiting
Department of Surgery
Roskilde, 4000
Ismail Gögenur, MD, DMSc, +45 26336426, igo@regionsjaelland.dk
Rasmus P Vogelsang, MD, +45 27351103
About this study
Official title: Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE).
Read the detailed description
Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumor cells more porous which allows the drug easier access into the cancer cells, whereas other tissues and organs in the body remain relatively poor at absorbing the drug, thereby reducing the potential side effects on healthy tissues. Procedures with electrochemotherapy have previously been applied to human patients in other countries of the EU, the US and Japan.
The drug concentration used is significantly reduced due to the more targeted absorption by the tumor and this significantly reduces side effects normally associated with chemotherapy.
A large number of preclinical and clinical Phase I and I/II studies have demonstrated the efficiency and safety of ECT. These studies have included patients with melanoma, head and neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma nodules.
An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors has recently been developed. The treatment procedure is similar to standard endoscopic colorectal examination (therapeutic colonoscopy) with the added element of an intravenous injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire procedure is minimally invasive and completely ambulatory. A successful treatment will cause the tumor to shrink in size in the weeks following the procedure.
The objective of this study is to investigate the efficacy and safety of this approach in downsizing locally advanced rectal tumors prior to intended curative surgery.
Time frame:
- All patients will be treated with standard neoadjuvant chemoradiation therapy prior to enrollment in this trial.
- Alle patients will have PET/MRI scans performed twice to evaluate treatment response (before and after ECT)
- ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.
- Alle patients will be followed up for 3 months.
- Being tested
- Electrochemotherapy with bleomycin, EndoVE
- Keywords
- Neoplasms, Neoplasms, primary, Cancer, Colorectal cancer, rectal cancer, rectal cancer, locally advanced, Electrochemotherapy, Electroporation, Neoadjuvant therapy, Antineoplastic, antibodies, Bleomycin, Pathologic processes, Neoplastic processes
- Medical subject headings
- Neoplasms, Colorectal Neoplasms, Rectal Neoplasms, Pathologic Processes, Neoplastic Processes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrochemotherapy with bleomycinDrug
Also called ATC code L01DC01, EV substance code SUB00844MIG
Systemic injection, once only treatment
EndoVEDevice
Also called Endoscopic electroporation
Electroporation using an endoscopic electroporation device
| Study group | Role | What they receive |
|---|---|---|
| Electrochemotherapy with bleomycin | Experimental | Systemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA.
BSA by Du Bois formula. Receives: Drug: Electrochemotherapy with bleomycin; Device: EndoVE |
| Standard care | No intervention | Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histopathologic tumor regression following electrochemotherapy
Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)
Measured: 4 weeks
Secondary outcomes (4)
Treatment safety of electrochemotherapy
Number of participants with treatment-related adverse events as assesed by CTCAE version 4.0
Measured: 4 months
Treatment safety of surgery following electrochemotherapy
Number of participants with compromized surgery following electrochemotherapy assesed by R1 resection rate, CRM involvement, non-mesorectal resection plane, and post operative complications according to Clavien-Dindo Classification
Measured: 4 weeks
Tumor regression according to Hybrid PET/MRI following electrochemotherapy
Tumor regression as assesed by tumor stage (T-stage)
Measured: 4 weeks
Tumor Immunologic response following electrochemotherapy
Tumor immunologic infiltration as assesed by the Immunoscore through immunohistochemical analysis
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study startJan 2017
- Primary completionJun 2019 (estimated)
- Study completionSep 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Rectal CancerStudies of the same condition, open and under way.
- More trials run by Zealand University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zealand University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Herlev Hospital, Copenhagen University Hospital, Rigshospitalet
- Responsible party
- Sponsor
- Investigators
- Ismail Gögenur, Professor, Principal investigator, Department of Surgery, Zealand University HospitalJulie Gehl, MD, DMSc, Principal investigator, Department of Oncology, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03040180
- Sponsor's protocol ID
- REG-32-2016
- Acronym
- nECT
- Status last verified
- Jan 2019
- First submitted
- 25 Jan 2017
- Last updated
- 25 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endoscopic Assisted Electrochemotherapy in Addition to Neoadjuvant Treatment of Locally Advanced Rectal Cancer: a Randomized Clinical Phase II Trial
- ClinicalTrials.gov ID
- NCT03040180
- Acronym / sponsor ID
- nECT / REG-32-2016
- Keywords
- Neoplasms, Neoplasms, primary, Cancer, Colorectal cancer, rectal cancer, rectal cancer, locally advanced, Electrochemotherapy, Electroporation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Zealand University HospitalUniversity, hospital or other
- Collaborators
- Herlev Hospital, Copenhagen University Hospital, Rigshospitalet
- Study start
- Jan 2017 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Sep 2019 (estimated)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant electrochemotherapy on locally advanced rectal cancer (UICC II-III) in an intended curative clinical setting, using an endoscopic electroporation device (EndoVE).
Detailed description
Electroporation of cancer cells allows for a greater concentration of chemotherapy drugs to enter the tumor cells. The uptake of the chemotherapeutic drug is aided through the application of short electric pulses to the tumor mass (referred to as - Electrochemotherapy or ECT). The pulses make the tumor cells more porous which allows the drug easier access into the cancer cells, whereas other tissues and organs in the body remain relatively poor at absorbing the drug, thereby reducing the potential side effects on healthy tissues. Procedures with electrochemotherapy have previously been applied to human patients in other countries of the EU, the US and Japan.
The drug concentration used is significantly reduced due to the more targeted absorption by the tumor and this significantly reduces side effects normally associated with chemotherapy.
A large number of preclinical and clinical Phase I and I/II studies have demonstrated the efficiency and safety of ECT. These studies have included patients with melanoma, head and neck squamous cell carcinoma, merkel cell carcinomas, basal cell carcinoma and adenocarcinoma nodules.
An endoscopic system (EndoVE ) for delivering the electric pulses to gastrointestinal tumors has recently been developed. The treatment procedure is similar to standard endoscopic colorectal examination (therapeutic colonoscopy) with the added element of an intravenous injection of bleomycin followed by the delivery of electric pulses (each one less than 1msec in duration). The pulses are endoscopically delivered directly to the tumor mass. The entire procedure is minimally invasive and completely ambulatory. A successful treatment will cause the tumor to shrink in size in the weeks following the procedure.
The objective of this study is to investigate the efficacy and safety of this approach in downsizing locally advanced rectal tumors prior to intended curative surgery.
Time frame:
- All patients will be treated with standard neoadjuvant chemoradiation therapy prior to enrollment in this trial.
- Alle patients will have PET/MRI scans performed twice to evaluate treatment response (before and after ECT)
- ECT treatment will be performed 4 weeks prior to surgery outlined by MDT.
- Alle patients will be followed up for 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Electrochemotherapy with bleomycin | Experimental | Drug: Electrochemotherapy with bleomycin, Device: EndoVESystemic injection of bleomycin followed by electroporation of the primary tumor. Bleomycin administration: 15.000 IU/m2 BSA. BSA by Du Bois formula. |
| Standard care | No intervention | –Standard care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient must be mentally capable of understanding the information given.
- Patients must give written informed consent.
- Men or women aged at least 18 years.
- Histologically verified rectal tumor (adenocarcinoma)
- Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with neoadjuvant therapy followed by surgical excision (UICC stadium II-III).
Key exclusion criteria (21 listed)
- Coagulation disorders
- Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
- Patients with ICD or pacemaker units.
- Patients with epilepsy.
- Pregnancy or lactation/breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electrochemotherapy with bleomycinAlso: ATC code L01DC01, EV substance code SUB00844MIGSystemic injection, once only treatment | Drug | Electrochemotherapy with bleomycin |
| EndoVEAlso: Endoscopic electroporationElectroporation using an endoscopic electroporation device | Device | Electrochemotherapy with bleomycin |
Primary outcome
Histopathologic tumor regression following electrochemotherapy
Time frame: 4 weeks
Number of participants with histopathologic tumor regression following elctrochemotherapy as assesed by histopathological evaluation of Tumor Regression Grade (Mandard Classification, TRG 1-5)
4 secondary outcomes
Treatment safety of electrochemotherapy
Time frame: 4 months
Treatment safety of surgery following electrochemotherapy
Time frame: 4 weeks
Tumor regression according to Hybrid PET/MRI following electrochemotherapy
Time frame: 4 weeks
Tumor Immunologic response following electrochemotherapy
Time frame: 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2019.
- Individual participant dataSharing planned: Undecided. Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ismail Gögenur, Professor principal investigator
Department of Surgery, Zealand University Hospital
Julie Gehl, MD, DMSc principal investigator
Department of Oncology, Herlev Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Electrochemotherapy with bleomycin and EndoVE in people with Locally Advanced Rectal Cancer and Electrochemotherapy, run by Zealand University Hospital at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ismail Gögenur, MD, DMSc (+45 26336426, igo@regionsjaelland.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histopathologic tumor regression following electrochemotherapy (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2019.